GENETIC EPIDEMILOGY OF ENGERGY METABOLISM IN BLACK GIRLS

黑人女孩能量代谢的遗传流行病学

• 批准号: 6746068
• 负责人: SUE Y.S. KIMM
• 金额: $ 33.74万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746068
• 关键词: African American; adolescence (12-20); alleles; basal metabolism; beta adrenergic receptor; bioenergetics; body composition; epidemiology; family genetics; fats; female; gene expression; gene interaction; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human subject; membrane proteins; mitochondrial membrane; morphometry; obesity; photon absorptiometry; questionnaires; women' s health

DESCRIPTION: The high prevalence of obesity in African-American (AA) women is of public health importance since AA women suffer higher mortality from cardiovascular and renal diseases than do white (W) women. The reason for their marked susceptibility to obesity remains poorly understood though it is now known that AA women manifest lower resting energy expenditure (REE) than W women. We propose a multi-pronged metabolic and genetic epidemiologic study to examine two candidate genes (UCP3 and b3AR) implicated in energy metabolism which have yet to be investigated in this high risk group. This application builds upon the findings from our previous study of a biracial cohort of 150 young women aged 19-21. We showed that REE (adjusted for fat mass and fat-free mass) in AA women was consistently lower than W by about 78 kcal/day across the entire range of adiposity. Further, REE was lower for those AA women homozygous for the C allele of UCP3 (exon 5). However, due to the relative rarity of the C allele among AA, our sample size of 5 AA homozygous for C allele yielded only a weak association, p=0.05. We propose to screen 600 AA girls, aged 12-15 years, using buccal swabs as a non-invasive method of obtaining DNA, to determine their UCP3 genotypes as well as b3AR genotypes. We will recruit 211 girls, selected based on their UCP3 genotype, for measurements of REE and body composition (using DEXA) in a controlled setting of the Clinical Research Center at the Cincinnati Children's Hospital. We will examine variation in REE across the genotypes of UCP3 with a large sample to corroborate our previous finding. The proposed 2x3 design will allow us to examine whether the effects associated with UCP3 variation are due to the UCP3 locus alone or due to the additive effect or interaction between UCP3 and b3AR. This has not been considered before. Our study will help to better understand the relationship between variation in two important candidate genes for energy metabolism, UCP3 and b3AR, and inter-individual variation in the levels of REE in this very high risk (for obesity) population. This application also builds on a well-established collaborative relationship between the PI and the researchers at the Cincinnati Children's Hospital and also with Dr. Ferrell's Human Genetics Laboratory at the University of Pittsburgh. Thus, information obtained from the proposed study should increase our understanding of the complex interrelationship between ethnicity, genetics, energy metabolism, and obesity development. This, in turn, should help advance our quest for "thrifty" genes, since parsimonious energy expenditure may be the main phenotypic manifestation of such a genotype.

描述：非洲裔美国人（AA）妇女的肥胖症患病率很高 公共健康的重要性，因为AA妇女因遭受更高的死亡而 与白人（W）女性相比，心血管和肾脏疾病。他们的原因 尽管现在是明显的易感性 知道妇女比W相比表现出较低的休息能量消耗（REE） 女性。我们提出了一项多管齐的代谢和遗传流行病学研究 检查与能量代谢有关的两个候选基因（UCP3和B3AR） 在这个高风险组中尚待调查。此应用程序 建立在我们先前对混血儿队150的研究的发现的基础上 19-21岁的年轻妇女。我们证明了REE（针对脂肪质量和无脂肪调整 质量）在AA中，妇女始终低于W的妇女，约78 kcal/day 全部肥胖范围。此外，那些AA女性纯合子的REE较低 对于UCP3的C等位基因（外显子5）。但是，由于C的相对稀有性 AA中的等位基因，我们的样本量为5 AA的纯合子等位基因仅产生A 弱关联，p = 0.05。我们建议筛选600名AA女孩，年龄12-15岁， 使用颊拭子作为获得DNA的非侵入性方法，以确定 他们的UCP3基因型以及B3AR基因型。我们将招募211个女孩， 根据其UCP3基因型选择，用于测量REE和身体 在临床研究的受控环境中的组成（使用dexa） 辛辛那提儿童医院中心。我们将检查REE的变化 在UCP3的基因型中，有大量样本来证实我们的先前 发现。提出的2x3设计将使我们能够检查效果是否 与UCP3变化相关的是由于单独的UCP3基因座或 UCP3和B3AR之间的添加效果或相互作用。这不是 考虑到之前。我们的研究将有助于更好地了解关系 在两个重要的候选基因的变异之间，能量代谢，UCP3 和B3AR，以及在这个非常高的REE水平的个体差异 风险（肥胖）人口。该应用程序还基于 PI与研究人员之间建立了良好的协作关系 在辛辛那提儿童医院，以及费雷尔博士的人 匹兹堡大学的遗传实验室。因此，获得的信息 根据拟议的研究，应提高我们对复杂的理解 种族，遗传学，能量代谢和肥胖之间的相互关系 发展。反过来，这应该有助于提高我们对“节俭”基因的追求， 由于简约的能量消耗可能是主要的表型表现 这种基因型。